Sepiapterin reductase

Sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)

PDB rendering based on 1z6z.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1Z6Z, 4HWK, 4J7U, 4J7X

Identifiers

Symbols

SPR ; SDR38C1

External IDs

OMIM: 182125 MGI: 103078 HomoloGene: 37735 GeneCards: SPR Gene

EC number

1.1.1.153

Gene ontology
Molecular function	• aldo-keto reductase (NADP) activity • sepiapterin reductase activity • NADP binding
Cellular component	• nucleoplasm • cytoplasm • mitochondrion • cytosol • extracellular exosome
Biological process	• L-phenylalanine metabolic process • tetrahydrobiopterin biosynthetic process • nitric oxide biosynthetic process • death • pteridine metabolic process • regulation of multicellular organism growth • norepinephrine metabolic process • dopamine metabolic process • serotonin metabolic process • small molecule metabolic process • nitric oxide metabolic process • cell morphogenesis involved in neuron differentiation • voluntary musculoskeletal movement • regulation of nitric-oxide synthase activity • oxidation-reduction process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 2:
72.89 – 72.89 Mb

Chr 6:
85.13 – 85.14 Mb

PubMed search

Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene.^[1]^[2]^[3]

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases. SPR plays an important role in the biosynthesis of tetrahydrobiopterin.^[3]

Reaction

sepiapterin reductase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

Sepiapterin reductase (SPR) catalyzes the chemical reaction

L-erythro-7,8-dihydrobiopterin + NADP+ $\rightleftharpoons$ sepiapterin + NADPH + H+

Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP⁺, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H⁺).

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP⁺ oxidoreductase. This enzyme participates in folate biosynthesis.

^[4]

References

↑ Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (Oct 1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochem Biophys Res Commun 179 (1): 183–189. doi:10.1016/0006-291X(91)91352-D. PMID 1883349.
↑ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact 178 (1–3): 94–98. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
1 2 "Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP⁺ oxidoreductase)".
↑ http://brenda-enzymes.info/enzyme.php?ecno=1.1.1.153

Katoh S (1971). "Sepiapterin Reductase from Horse Liver: Purification and Properties of the Enzyme.". Arch. Biochem. Biophys. 146 (1): 202–214. doi:10.1016/S0003-9861(71)80057-7. PMID 4401291.
Matsubara M, Katoh S, Akino M, Kaufman S (1966). "Sepiapterin Reductase.". Biochim. Biophys. Acta 122 (2): 202–212. doi:10.1016/0926-6593(66)90062-2. PMID 5969298.
Takikawa S, Curtius HC, Redweik U, et al. (1987). "Biosynthesis of tetrahydrobiopterin. Purification and characterization of 6-pyruvoyl-tetrahydropterin synthase from human liver". Eur. J. Biochem. 161 (2): 295–302. doi:10.1111/j.1432-1033.1986.tb10446.x. PMID 3536512.
Thöny B, Heizmann CW, Mattei MG (1995). "Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization". Genomics 26 (1): 168–170. doi:10.1016/0888-7543(95)80101-Q. PMID 7782081.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Maier J, Schott K, Werner T, et al. (1994). "Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and tissues". Adv. Exp. Med. Biol. 338: 195–8. doi:10.1007/978-1-4615-2960-6_39. PMID 8304109.
Maier J, Schott K, Werner T, et al. (1993). "Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species". Exp. Cell Res. 204 (2): 217–222. doi:10.1006/excr.1993.1027. PMID 8440319.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Blau N, Thöny B, Renneberg A, et al. (1998). "Dihydropteridine reductase deficiency localized to the central nervous system". J. Inherit. Metab. Dis. 21 (4): 433–434. doi:10.1023/A:1005327313348. PMID 9700606.
Ohye T, Hori TA, Katoh S, et al. (1998). "Genomic organization and chromosomal localization of the human sepiapterin reductase gene". Biochem. Biophys. Res. Commun. 251 (2): 597–602. doi:10.1006/bbrc.1998.9503. PMID 9792819.
Blau N, Thöny B, Renneberg A, et al. (1999). "Variant of dihydropteridine reductase deficiency without hyperphenylalaninaemia: effect of oral phenylalanine loading". J. Inherit. Metab. Dis. 22 (3): 216–220. doi:10.1023/A:1005584627797. PMID 10384371.
Bonafé L, Thöny B, Penzien JM, et al. (2001). "Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia". Am. J. Hum. Genet. 69 (2): 269–277. doi:10.1086/321970. PMC 1235302. PMID 11443547.
Fujimoto K, Takahashi SY, Katoh S (2002). "Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca<sup2+/calmodulin-dependent protein kinase II". Biochim. Biophys. Acta 1594 (1): 191–8. doi:10.1016/S0167-4838(01)00300-4. PMID 11825621.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Franscini N, Bachli EB, Blau N, et al. (2005). "Functional tetrahydrobiopterin synthesis in human platelets". Circulation 110 (2): 186–192. doi:10.1161/01.CIR.0000134281.82972.57. PMID 15197144.
Steinberger D, Blau N, Goriuonov D, et al. (2005). "Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene (SPR) in a patient with dopa-responsive dystonia". Neurogenetics 5 (3): 187–190. doi:10.1007/s10048-004-0182-3. PMID 15241655. replacement character in |last7= at position 2 (help)
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Sharma M, Mueller JC, Zimprich A, et al. (2006). "The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations". J. Med. Genet. 43 (7): 557–562. doi:10.1136/jmg.2005.039149. PMC 2593029. PMID 16443856.
Farrugia R, Scerri CA, Montalto SA, et al. (2007). "Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population". Mol. Genet. Metab. 90 (3): 277–283. doi:10.1016/j.ymgme.2006.10.013. PMID 17188538.
Tobin JE, Cui J, Wilk JB, et al. (2007). "Sepiapterin reductase expression is increased in Parkinson's disease brain tissue". Brain Res. 1139: 42–47. doi:10.1016/j.brainres.2007.01.001. PMC 1868471. PMID 17270157.

PDB gallery

1z6z: Crystal Structure of Human Sepiapterin Reductase in complex with NADP+

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

Metabolism of vitamins, coenzymes, and cofactors

Fat soluble vitamins

Vitamin A	Retinol binding protein

Vitamin E	Alpha-tocopherol transfer protein

Vitamin D	liver (Sterol 27-hydroxylase or CYP27A1) renal (25-Hydroxyvitamin D₃ 1-alpha-hydroxylase or CYP27B1) degradation (1,25-Dihydroxyvitamin D₃ 24-hydroxylase or CYP24A1)

Vitamin K	Vitamin K epoxide reductase

Water soluble vitamins

Thiamine (B₁)

Thiamine diphosphokinase

Niacin (B₃)

Pantothenic acid (B₅)

Pantothenate kinase

Folic acid (B₉)

Dihydropteroate synthase Dihydrofolate reductase Serine hydroxymethyltransferase

Methylenetetrahydrofolate reductase

Vitamin B₁₂

Vitamin C

L-gulonolactone oxidase

Riboflavin (B₂)

Riboflavin kinase

Nonvitamin cofactors

Tetrahydrobiopterin

GTP cyclohydrolase I 6-pyruvoyltetrahydropterin synthase Sepiapterin reductase

PCBD1 PTS QDPR

Molybdenum cofactor

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Sepiapterin reductase

Function

Reaction

References

Further reading